A knowledge of the molecular events involed in the formation of chromosome aberrations is fundamental to the understanding of a variety of biological phenomena including mutations, malignant transformation, loss of cell viability, and birth defects. In the past, however, such understanding has been hampered by the inability to determine which DNA lesions result in chromosome aberrations. The purpose of this proposal is to elucidate the molecular mechanisms of chromosome aberration formation through a multiparameter approach which will allow correlation between specific DNA lesions and specific aberration types. Under this project, we plan to use four recently developed technologies (i.e. DNA repair deficient cell lines, DNA modifying enzymes, alkaline elution and premature chromosome condensation) to do the following: (1) Correlate the kinetics of repair of particular DNA lesions with chromosome repair; (2) obtain cells with a single type of DNA lesion and determine how this lesion is translated into a chromosome aberration; and (3) determine what in vivo enzymatic manipulations are required to turn a defined DNA lesion into a chromosome aberration.